Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For the patient suffering from severe disabling psoriasis, there is now a choice of three possible therapeutic modalities: PUVA, retinoid, or cystostatics. We have had the most experience with methotrexate, as it has been used to treat psoriasis for more than 30 years. For this reason, there is also extensive experience with regard to the risk benefit ratio for this drug. Treatment with methotrexate requires normal kidney function, liver, and bone marrow function. Pregnancy is an absolute contraindication. Methotrexate is hepatotoxic. Fibrosis and cirrhosis are not uncommon when the cumulative dosage exceeds 1.5 g; methotrexate-induced liver cirrhosis is not, however, a rapidly progressing disease. Treatment with methotrexate requires regular laboratory control, and experience to date also indicates that liver biopsy specimens should be taken during treatment.
 ...
PMID:[Oral methotrexate therapy: pro and con]. 397 75

Of 21 patients with rheumatoid arthritis who began to receive low-dose weekly methotrexate up to five years ago, 15 (71 percent) have continued to take this drug for a mean of 42 months and have received a mean total dose of 2,021 mg (range: 915 to 3,075). The clinical improvement noted at the first follow-up (11 months) was sustained throughout this follow-up period (42 months). Three patients (14 percent) have had complete clinical remission and nine others (43 percent) have had an excellent response. Methotrexate was discontinued in four patients between the first and second follow-up because of planned pregnancy (one), gastrointestinal toxicity (two), and fear of toxicity (one). Liver toxicity assessed in these 21 patients and four others receiving long-term methotrexate therapy revealed acute hepatitis in one and elevated transaminase levels in 12 (48 percent). Liver biopsy specimens in 17 patients after a mean of 1,950 mg of methotrexate (range: 915 to 3,125) revealed mild fibrosis in six and no cirrhosis. Methotrexate can continue to suppress rheumatoid synovitis over a prolonged period of time with minimal toxicity in most patients. Hepatic fibrosis and cirrhosis due to methotrexate may be less common in rheumatoid arthritis than has been reported in psoriasis.
 ...
PMID:Low-dose methotrexate treatment of rheumatoid arthritis. Long-term observations. 403 84

Methotrexate has been associated with chronic toxicities such as cirrhosis and neurological impairments ranging from mild learning disorders to a fatal leucoencephalopathy. The mechanism(s) for this toxicity is not completely understood. Certain tissues can convert methotrexate to polyglutamates. This results in a more persistent intracellular form of the drug. In this study the intracellular levels of folate and methotrexate were measured in the erythrocytes and liver of patients treated chronically with methotrexate. These tissues showed an accumulation of methotrexate as polyglutamates and a concomitant loss of folate. Folate concentrations were below normal in nine of 12 red cell and three of five liver samples. It is proposed that persistent methotrexate concentrations and/or the associated folate deficiency may be related to the toxicity of methotrexate, especially in time of cellular stress.
 ...
PMID:Methotrexate accumulation and folate depletion in cells as a possible mechanism of chronic toxicity to the drug. 617 Mar 7

Methotrexate in a low dose intermittent regimen has become popular as a therapeutic choice for refractory psoriatic arthritis, polymyositis, Reiter's disease and more recently rheumatoid arthritis. As a folate analogue, it inhibits the formation of reduced folate cofactors which participate in a host of important reactions including DNA synthesis. It has been shown to have both immunosuppressive and anti-inflammatory properties although its precise mechanism of action in these diseases is not known. It may be variably absorbed especially in psoriatics and its action may be antagonized by folate supplements. Its major route of metabolism appears to be via the enterohepatic circulation. Numerous drugs, including salicylates, may increase serum levels by displacing the drug from protein binding sites and by competing for renal excretion. It has fewer short term side effects than the other immunosuppressives used in rheumatic disease. Its major long term toxicity is liver fibrosis or cirrhosis which appears to increase with greater cumulative dosage and treatment duration. Several recent reports of hypersensitivity pneumonitis reinforce the previous literature on this topic. Pulmonary toxicity may be more common than suggested as more patients are treated with methotrexate for rheumatic diseases. Clinical studies in general have been uncontrolled and lacking in scope and size. Nevertheless, the literature to date appears to show this to be an excellent drug for use in the diseases mentioned. Prospective double blind controlled studies on psoriatic arthritis and rheumatoid arthritis should help establish this drug as the immunosuppressive of choice in these diseases.
 ...
PMID:Methotrexate: its use in the rheumatic diseases. 639 73

Methotrexate is widely used by dermatologists in the treatment of recalcitrant psoriasis. Despite potentially serious side effects, including hepatic cirrhosis, the drug is relatively safe and remarkably effective when carefully administered to selected patients.
 ...
PMID:Methotrexate in psoriasis. A brief review of indications, usage, and complications of methotrexate therapy. 736 74

The recently recognized high morbidity and unexpected mortality associated with rheumatoid arthritis (RA) has spurred new interest in more aggressive, early treatment of this disease. Methotrexate (MTX) has rapidly become the rheumatologist's drug of choice for serious RA because of its favorable efficacy to toxicity ratio and rapid onset of action compared with other second-line agents. The initial concerns about hepatic fibrosis and cirrhosis in psoriatic patients has subsided somewhat as long-term liver toxicity data are accumulating in patients with RA. Routine liver biopsy with incremental doses of MTX is no longer recommended. Potential for severe lung, hematologic, and infectious complications exists, mandating careful monitoring of RA patients taking MTX.
 ...
PMID:Methotrexate: the emerging drug of choice for serious rheumatoid arthritis. 769 87

Methotrexate is the drug with the highest long-term continuation rate in rheumatoid arthritis patients. However, toxicity is the main reason for methotrexate withdrawal. Most adverse effects are mild abnormalities, such as digestive symptoms, stomatitis, elevations in transaminase levels, and moderate decreases in peripheral blood cell counts. Potentially life-threatening effects include hypersensitivity pneumonitis and pancytopenia. Cirrhosis is less common than in patients with psoriasis. Opportunistic infections and Epstein-Barr virus-related lymphomas have been reported. Neurological disorders, cutaneous reactions and renal lesions have been ascribed to low-dose methotrexate. Prior renal dysfunction and concomitant administration of a number of drugs, including cotrimoxazole, have been shown to increase methotrexate toxicity. However, susceptibility to the toxic effects of methotrexate varies widely across individuals. The effectiveness of folate supplementation in preventing methotrexate toxicity remains controversial.
 ...
PMID:[Side-effects during treatment of rheumatoid arthritis with methotrexate]. 781 88

Over the last several years, information on methotrexate's mechanism(s) of action (which affects its efficacy) and toxicities continue to evolve. This popular second line agent (DMARD) is a potent anti-inflammatory drug, with effects on LTB4 and adenosine release (EC-50: 1-13 nM). As such, it may be a sufficiently potent anti-inflammatory drug to affect rheumatoid arthritis's basic course, as shown by a recent meta-analysis where methotrexate equalled gold and was better than azathioprine, when examining radiographic erosions. Its toxicities continue to be documented, with cirrhosis occurring between 2:100 and 1:1000 cases. Pneumonitis continues to be found. NSAID-MTX interactions, too, have been documented, although their kinetic mechanisms remain controversial.
 ...
PMID:Methotrexate: new mechanisms and old toxicities. 839 46

Juvenile Rheumatoid Arthritis (JRA) is a chronic, inflammatory, autoimmune disease of childhood. Methotrexate is an emerging antirheumatic drug in the pediatric population for disease refractory to conventional medications. While observations are encouraging, the toxic side effects can be potentially serious. Toxicity includes gastrointestinal intolerance, ulcerative stomatitis, chemical hepatitis, minor liver fibrosis, infection, hematologic suppression, acute pneumonitis, reversible oligospermia, and cirrhosis. The liver toxicities are of the greatest concern. If proper dosage and monitoring are followed, serious toxic effects can be prevented from occurring.
 ...
PMID:Methotrexate use in juvenile rheumatoid arthritis. 845 Oct 58

Methotrexate's mechanism of action affects both the inflammatory and immunosuppressive aspects of response. Its kinetics are defined and include variable absorption, intracellular metabolism, and both renal and biliary excretion. Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions. It is also effective in psoriatic arthritis and is being used in a multiplicity of other rheumatic diseases. The most common toxicities ascribed to methotrexate are gastrointestinal (e.g. stomatitis) and central nervous system (e.g. headache, fatigue, malaise). Methotrexate-induced hepatic cirrhosis is less common in rheumatoid arthritis than previously thought, although its occurrence in psoriasis is probably higher than in rheumatoid arthritis. Haematological, renal and pulmonary toxicity occur, but are rare, while teratogenicity is well documented. A new and disturbing adverse event, pseudolymphomas are being reported at present.
 ...
PMID:The rational use of methotrexate in rheumatoid arthritis and other rheumatic diseases. 971 72


<< Previous 1 2 3 4 Next >>